This is a revised proposal to purchase a Computer Cluster to support nine NIH funded investigators carrying out research in computational and structural biology, structural genomics, and proteomics. We propose to acquire a 150 processor cluster based on the Linux operating system and the Opteron 280 AMD 64 bit dual-core processor. This is a much more cost efficient processor than the one available when the original proposal was submitted in March 2005; so that we are able to reduce the budget request by 40% without a significant decrease in the performance of the cluster we propose to acquire. Additionally, we provide more detailed information about the current computer facilities and the urgent need of these investigators to obtain NIH support to acquire the proposed instrument which will be used to update, centralize, and integrate the computational facilities which support the NIH funded projects described in this proposal. The projects for which the requested equipment will be used include: Effective Potentials and Sampling Methods for Protein Folding and Binding (R. Levy and E. Gallicchio), RNase H Inhibitors Targeting a Novel Site on HIV-1 RT (E. Arnold), NMR Investigation of Protein Folding and Misfolding (J. Baum), Automated NMR Protein Structure Determination and Refinement (G. Montelione), Multi-scale Modeling of Nucleic Acids (W. Olson), Structural Studies of RNA Polymerase Transcription Complexes and RNAP- Antibiotic Interactions (R. Ebright, E. Arnold, H. Berman), Parallel Single Molecule Data Analysis (D. Talaga), and Bioinformatic Modeling of Protein Interaction and Gene Regulation Networks (A. Sengupta). The projects described in this proposal all have computationally intensive components and due to their distributed and coarse-grained parallel nature, will greatly benefit from access to state-of-the-art hardware and a larger number of processors than is currently available to these investigators. The public health-related relevance of the projects described in this proposal is highlighted in the two major goals of these projects. One goal is to further the understanding of aberrant structures of proteins that characterize misfolding disease states characteristic of Parkinson's, Alzheimer's, and similar diseases. A second major goal is to improve methods for the characterization of protein structures and assemblies as a basis for improving methods of structure based drug design for treatments of AIDS and other diseases. [unreadable] [unreadable] [unreadable]